کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2151443 | 1089993 | 2013 | 20 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The Roles of Telomerase in the Generation of Polyploidy during Neoplastic Cell Growth
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
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چکیده انگلیسی
Polyploidy contributes to extensive intratumor genomic heterogeneity that characterizes advanced malignancies and is thought to limit the efficiency of current cancer therapies. It has been shown that telomere deprotection in p53-deficient mouse embryonic fibroblasts leads to high rates of polyploidization. We now show that tumor genome evolution through whole-genome duplication occurs in â¼15% of the karyotyped human neoplasms and correlates with disease progression. In a panel of human cancer and transformed cell lines representing the two known types of genomic instability (chromosomal and microsatellite), as well as the two known pathways of telomere maintenance in cancer (telomerase activity and alternative lengthening of telomeres), telomere dysfunction-driven polyploidization occurred independently of the mutational status of p53. Depending on the preexisting context of telomere maintenance, telomerase activity and its major components, human telomerase reverse transcriptase (hTERT) and human telomerase RNA component (hTERC), exert both reverse transcriptase-related (canonical) and noncanonical functions to affect tumor genome evolution through suppression or induction of polyploidization. These new findings provide a more complete mechanistic understanding of cancer progression that may, in the future, lead to novel therapeutic interventions.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neoplasia - Volume 15, Issue 2, February 2013, Pages 156-168, IN11-IN17
Journal: Neoplasia - Volume 15, Issue 2, February 2013, Pages 156-168, IN11-IN17
نویسندگان
Agni Christodoulidou, Christina Raftopoulou, Maria Chiourea, George K. Papaioannou, Hirotoshi Hoshiyama, Woodring E. Wright, Jerry W. Shay, Sarantis Gagos,